Analysis of intensity normalization for optimal segmentation performance of a fully convolutional neural network.

INTRODUCTION Convolutional neural networks have begun to surpass classical statistical- and atlas based machine learning techniques in medical image segmentation in recent years, proving to be superior in performance and speed. However, a major challenge that the community faces are mismatch between variability within training and evaluation datasets and therefore a dependency on proper data pre-processing. Intensity normalization is a widely applied technique for reducing the variance of the data for which there are several methods available ranging from uniformity transformation to histogram equalization. The current study analyses the influence of intensity normalization on cerebellum segmentation performance of a convolutional neural network (CNN). METHOD The study included three population samples with a total number of 218 datasets, all including a T1w MRI data set acquired at 3T and a ground truth segmentation delineating the cerebellum. A 12 layer deep 3D fully convolutional neural network was trained using 150 datasets from one of the population samples. Four different intensity normalization methods were separately applied to pre-process the data, and the CNN was correspondingly trained four times with respect to the different normalization techniques. A quantitative analysis of the segmentation performance, assessed via the Sørensen-Dice similarity coefficient (DSC) of all four CNNs, was performed to investigate the intensity sensitivity of the CNNs. Additionally, the optimal network performance was determined by identifying the best parameter set for intensity normalization. RESULTS All four normalization methods led to excellent (mean DSC score=0.96) segmentation results when evaluated using known data; however, the segmentation performance differed depending on the applied intensity normalization method when testing with formerly unseen data, in which case the histogram equalization methods outperformed the unit distribution methods. A detailed, systematic analysis of intensity manipulations revealed, that the distribution of input intensities clearly affected the segmentation performance and that for each input dataset a linear intensity modification (shifting and scaling) existed leading to optimal segmentation results. This was further proven by an optimization analysis to find the optimal adjustment for an individual input evaluation sample within each normalization configuration. DISCUSSION The findings suggest that proper preparation of the evaluation data is more crucial than the exact choice of normalization method to prepare the training data. The histogram equalization methods tested in this study were found to perform this task best, although leaving room for further improvements, as shown by the optimization analysis.

[1]  Sergey Ioffe,et al.  Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift , 2015, ICML.

[2]  Li Bai,et al.  The influence of intensity standardization on medical image registration , 2010, Medical Imaging.

[3]  H. Fukuda,et al.  Segmentation of the hippocampus by transferring algorithmic knowledge for large cohort processing , 2018, Medical Image Anal..

[4]  C. Crainiceanu,et al.  Statistical normalization techniques for magnetic resonance imaging , 2014, NeuroImage: Clinical.

[5]  João Otávio Bandeira Diniz,et al.  Detection of white matter lesion regions in MRI using SLIC0 and convolutional neural network , 2018, Comput. Methods Programs Biomed..

[6]  Simon K. Warfield,et al.  Normalization of joint image-intensity statistics in MRI using the Kullback-Leibler divergence , 2004, 2004 2nd IEEE International Symposium on Biomedical Imaging: Nano to Macro (IEEE Cat No. 04EX821).

[7]  Jayaram K. Udupa,et al.  New variants of a method of MRI scale standardization , 2000, IEEE Transactions on Medical Imaging.

[8]  Victor Alves,et al.  Brain Tumor Segmentation Using Convolutional Neural Networks in MRI Images , 2016, IEEE Transactions on Medical Imaging.

[9]  John A. Nelder,et al.  A Simplex Method for Function Minimization , 1965, Comput. J..

[10]  L. R. Dice Measures of the Amount of Ecologic Association Between Species , 1945 .

[11]  D. Louis Collins,et al.  Evaluating intensity normalization on MRIs of human brain with multiple sclerosis , 2011, Medical Image Anal..

[12]  Li Bai,et al.  The role of intensity standardization in medical image registration , 2010, Pattern Recognit. Lett..

[13]  Bram van Ginneken,et al.  A survey on deep learning in medical image analysis , 2017, Medical Image Anal..

[14]  Torsten Rohlfing,et al.  Image Similarity and Tissue Overlaps as Surrogates for Image Registration Accuracy: Widely Used but Unreliable , 2012, IEEE Transactions on Medical Imaging.

[15]  Ganapathy Krishnamurthi,et al.  Multi-modal Brain Tumor Segmentation Using Stacked Denoising Autoencoders , 2015, Brainles@MICCAI.

[16]  Fred A. Hamprecht,et al.  Multi-modal Brain Tumor Segmentation using Deep Convolutional Neural Networks , 2014 .

[17]  Hao Chen,et al.  VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images , 2017, NeuroImage.

[18]  Michael Weiner,et al.  Robust atrophy rate measurement in Alzheimer's disease using multi-site serial MRI: Tissue-specific intensity normalization and parameter selection , 2010, NeuroImage.

[19]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[20]  Konstantinos Kamnitsas,et al.  DeepCut: Object Segmentation From Bounding Box Annotations Using Convolutional Neural Networks , 2016, IEEE Transactions on Medical Imaging.

[21]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[22]  Konstantinos Kamnitsas,et al.  Efficient multi‐scale 3D CNN with fully connected CRF for accurate brain lesion segmentation , 2016, Medical Image Anal..

[23]  Klaus H. Maier-Hein,et al.  Deep MRI brain extraction: A 3D convolutional neural network for skull stripping , 2016, NeuroImage.

[24]  Parashkev Nachev,et al.  Computer Methods and Programs in Biomedicine NiftyNet: a deep-learning platform for medical imaging , 2022 .

[25]  Christian Wachinger,et al.  DeepNAT: Deep convolutional neural network for segmenting neuroanatomy , 2017, NeuroImage.

[26]  Lin Shi,et al.  Automatic Segmentation of Acute Ischemic Stroke From DWI Using 3-D Fully Convolutional DenseNets , 2018, IEEE Transactions on Medical Imaging.

[27]  Jose Dolz,et al.  3D fully convolutional networks for subcortical segmentation in MRI: A large-scale study , 2016, NeuroImage.

[28]  Jörn Diedrichsen,et al.  A spatially unbiased atlas template of the human cerebellum , 2006, NeuroImage.

[29]  Pierrick Coupé,et al.  Author manuscript, published in "Journal of Magnetic Resonance Imaging 2010;31(1):192-203" DOI: 10.1002/jmri.22003 Adaptive Non-Local Means Denoising of MR Images with Spatially Varying Noise Levels , 2010 .

[30]  Daniel L. Rubin,et al.  Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions , 2017, Journal of Digital Imaging.